Long-term effects of dietary sodium intake on cytokines and neurohormonal activation in patients with recently compensated congestive heart failure

J Card Fail. 2009 Dec;15(10):864-73. doi: 10.1016/j.cardfail.2009.06.002.


Background: A growing body of evidence suggests that the fluid accumulation plays a key role in the pathophysiology of heart failure (HF) and that the inflammatory and neurohormonal activation contribute strongly to the progression of this disorder.

Methods and results: The study evaluated the long-term effects of 2 different sodium diets on cytokines neurohormones, body hydration and clinical outcome in compensated HF outpatients (New York Heart Association Class II). A total of 173 patients (105 males, mean age 72.5+/-7) recently hospitalized for worsening advanced HF and discharged in normal hydration and in clinical compensation were randomized in 2 groups (double blind). In Group 1, 86 patients received a moderate restriction in sodium (120mmol to 2.8g/day) plus oral furosemide (125 to 250mg bid); in Group 2, 87 patients: received a low-sodium diet (80mmol to 1.8g/day) plus oral furosemide (125 to 250mg bid). Both groups were followed for 12 months and the treatment was associated with a drink intake of 1000mL daily. Neurohormonal (brain natriuretic peptide, aldosterone, plasma rennin activity) and cytokines values (tumor necrosis factor-alpha, interleukin-6) were significantly reduced with a significant increase of the anti-inflammatory cytokine interleukin-10 at 12 months in normal, P < .0001) than low-sodium group. The low-sodium diet showed a significant activation of neurohormones and cytokines and worsening the body hydration, whereas moderate sodium restriction maintained dry weigh and improved outcome in the long term.

Conclusions: Our results appear to suggest a surprising efficacy of a new strategy to improve the chronic diuretic response by increasing Na intake and limiting fluid intake. This counterintuitive approach underlines the need for a better understanding of factors that regulate sodium and water handling in chronic congestive HF. A larger sample of patients and further studies are required to evaluate whether this is due to the high dose of diuretic used or the low-sodium diet.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Cytokines / metabolism*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Heart Failure / blood
  • Heart Failure / diet therapy*
  • Humans
  • Male
  • Neurotransmitter Agents / metabolism*
  • Sodium, Dietary / administration & dosage*
  • Sodium, Dietary / blood
  • Sodium, Dietary / therapeutic use
  • Time Factors


  • Biomarkers
  • Cytokines
  • Neurotransmitter Agents
  • Sodium, Dietary